POS0034 GENETIC FACTORS OF PREDISPOSITION TO JUVENILE IDIOPATHIC ARTHRITIS AND OTHER ARTICULAR PATHOLOGY IN BELARUSIAN POPULATION
Authors: H. Yatskiu, A. Tchitchko, A. Sukalo, R. Goncharova
Journal: Annals of the Rheumatic Diseases (2022)

Background Juvenile idiopathic arthritis (JIA) is a multifactorial autoimmune disease and. JIA exhibits clinical heterogeneity and is divided into seven phenotypic subtypes. The outcome of JIA is often difficult to predict, and differential diagnosis is significantly complicated by the variety of causes of joint pain and the similarity of the clinical picture of articular syndrome, especially in the early stages of disease development. Objectives to detect genetic markers, associated with the risk of developing JIA, its distinct subtypes and another joint pathology in children. Methods 951 individuals were divided into three cohorts: 281 children with JIA (mean age 9.14±4.84), 214 children with articular syndrome in case of another joint pathology (post-infectious, post-traumatic and reactive arthritis, osteochondropathy and arthralgia; mean age 9.50±4.75) and 456 healthy controls (mean age 14.36±2.54). The JIA patients were divided into subgroups according to IIAR classification criteria. 9 SNPs of 8 genes ( IL6 (rs1800795), IL6R (rs2228145 and rs4845618), STAT4 (rs7574865), TRAF1/C5 (rs3761847), RUNX1 (rs9979383), PTPN2 (rs2542151), PTPN22 (rs2476601), FOXP3 (rs2232365)) were genotyped using Real-time PCR or PCR-RFLP. Results The allele frequencies of the polymorphic loci of the FOXP3 (rs2232365), RUNX1 (rs9979383), PTPN2 (rs2542151), PTPN22 (rs2476601) genes in all three groups were comparable, indicating no association with the risk of development of joint pathology in children. It was shown that CC genotype at the rs1800795 locus of the IL6 gene is associated with JIA (OR 1.49 [1.05–2.13], p=0.026), while the GC genotype revealed protective effect (OR 0.69 [0.51–0.93], p=0.014). In addition, a weak association of GG homozygotes at the TRAF1/C5 locus (rs3761847) with the risk of developing JIA was found (OR 1.47 [1.00-2.16], p = 0.05). Homozygous GG genotype at the rs3761847 TRAF1/C5 and CC at the rs1800795 IL6 loci, as well as the corresponding G and C alleles, were associated with early JIA onset (under the age of 6 years). At the same time, CC homozygotes (OR 2.45 [1.50–3.97], p=0.0003) and C allele (OR 1.33 [1.05–1.69], p=0, 02) at the rs2228145 locus, as well as TT homozygotes (OR 1.54 [1.06–2.23], p = 0.026) at the rs4845618 locus of the IL6R gene were associated with joint pathology except JIA. Moreover, minor alleles, as well as the corresponding homozygous genotypes of polymorphic IL6R loci were significantly more common among children with other articular pathology when compared with the JIA cohort. The association revealed for the CC genotype at the rs1800795 locus of the IL6 gene in the general JIA group preserved in the group of oligoarticular JIA (OR 1.59 [1.04–2.41], p=0.033) while GG genotype at rs3761847 locus of the TRAF1/C5 gene was associated with systemic JIA (OR 2.82 [1.29 – 6.15]; p = 0.013), and rheumatoid factor-negative polyarthritis was characterized by higher frequency of GT/TT genotypes at the STAT4 rs7574865 locus (OR 1.85 [1.06–3.24], p = 0.03). Conclusion Thus, the IL6 gene polymorphism increases the sensitivity of the Belarusian population to JIA, while the IL6R gene polymorphism affects the development of other joint pathology. It was found that JIA subtypes significantly differ from each other by the molecular profiles of non-HLA genes. This suggests that JIA is represented by a spectrum of genetically distinct subtypes that differ in clinical course and response to therapy. Acknowledgements This research was supported by The Research Technical Program “DNA Identification” (2017–2021), project number: 6.4 Disclosure of Interests None declared